Genetic Variant SPATA17:p.Asn288Ile (chr1-217782313-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138796.4(SPATA17):c.863A>T(p.Asn288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,608,006 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

SPATA17
NM_138796.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.00

Variant links:

Genes affected

SPATA17 (HGNC:25184): (spermatogenesis associated 17) Predicted to enable calmodulin binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPATA17 links:

SPATA17-AS1 (HGNC:41086): (SPATA17 antisense RNA 1)

SPATA17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009138256).

BP6

Variant 1-217782313-A-T is Benign according to our data. Variant chr1-217782313-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639902.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA17	NM_138796.4 link	c.863A>T	p.Asn288Ile	missense_variant	Exon 8 of 11	ENST00000366933.5	NP_620151.1	Q96L03
SPATA17	NM_001375655.1 link	c.863A>T	p.Asn288Ile	missense_variant	Exon 8 of 11		NP_001362584.1
SPATA17-AS1	NR_125784.1 link	n.160-14T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPATA17	ENST00000366933.5 link	c.863A>T	p.Asn288Ile	missense_variant	Exon 8 of 11	1	NM_138796.4	ENSP00000355900.4	Q96L03
SPATA17	ENST00000492747.2 link	n.709A>T		non_coding_transcript_exon_variant	Exon 5 of 6	5
SPATA17-AS1	ENST00000415765.1 link	n.160-14T>A		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

413

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00859

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000720

AC:

177

AN:

245686

Hom.:

AF XY:

0.000527

AC XY:

AN XY:

132952

show subpopulations

Gnomad AFR exome

AF:

0.00869

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000834

GnomAD4 exome

AF:

0.000323

AC:

470

AN:

1455692

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

212

AN XY:

724220

show subpopulations

Gnomad4 AFR exome

AF:

0.00970

Gnomad4 AMR exome

AF:

0.000949

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000451

Gnomad4 OTH exome

AF:

0.000815

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152314

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00863

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000424

Hom.:

Bravo

AF:

0.00337

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000931

AC:

113

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SPATA17: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.8

DANN

Benign

0.59

DEOGEN2

Benign

0.15

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0091

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.044

Sift

Benign

0.42

Sift4G

Benign

0.39

Polyphen

0.068

Vest4

0.27

MVP

0.14

MPC

0.030

ClinPred

0.011

GERP RS

2.4

Varity_R

0.20

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over